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| Bypass of senescence after disruption of p21(CIP1/WAF1) gene in normal diploid human fibroblasts |
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| Author(s): Brown JP, Wei WY, Sedivy JM |
| Source: SCIENCE Volume: 277 Issue: 5327 Pages: 831-834 Published: AUG 8 1997 |
| Times Cited: 377 References: 36 |
| Abstract: Most somatic cells die after a finite number of cell divisions, a phenomenon described as senescence. The p21(CIP1/WAF1) gene encodes an inhibitor of cyclin-dependent kinases. Inactivation: of p21 by two sequential rounds of targeted homologous recombination was sufficient to bypass senescence in normal diploid human fibroblasts. At the checkpoint between the prereplicative phase of growth and the phase of chromosome replication, cells lacking p21 failed to arrest the cell cycle in response to DNA damage, but their apoptotic response and genomic stability were unaltered. These results establish the feasibility of using gene targeting for genetic studies of normal human cells. |
| Document Type: Article |
| Language: English |
| Reprint Address: Brown, JP (reprint author), BROWN UNIV, DEPT BIOCHEM MOL BIOL & CELL BIOL, PROVIDENCE, RI 02912 USA |
| Publisher: AMER ASSOC ADVANCEMENT SCIENCE, 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: XQ247 |
| ISSN: 0036-8075 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |